This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We hypothesize that 4-HPR/LXS oral powder will: 1) allow drug administration to patients intolerant of the current NCI 4-HPR capsule, 2) produce more consistent, and possibly higher, 4-HPR plasma levels resulting in increased drug delivery to tumor cells, and 3) facilitate the testing of fenretinide-based drug combinations. SPECIFIC AIMS 1. To determine the maximun tolerated dose of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder (4-HPR/LXS oral powder) given orally, BID, for seven consecutive days every three weeks, in patients with recurrent and/or resistant neuroblastoma. 2. To define the toxicities of 4-HPR/LXS oral powder given on this schedule. 3. To determine the plasma pharmacokinetics of 4-HPR given on this schedule. Secondary Aims: 1. To determine the response rate to 4-HPR/LXS oral powder in patients with recurrent and/or resistant neuroblastoma within teh confines of a Phase I study. 2. To determine the level of 4-HPR delivered as 4-HPR/LXS oral powder in normal peripheral blood mononuclear cells (PBMC) as a tumor cell surrogate tissue. BACKGROUND AND SIGNIFICANCE Fenretinide (N-(4-hydroxyphenyl)retinamide, 4-HPR), is a cytotoxic retinoid that has activity against neuroblastoma cell lines in vitro in a dose-related manner. Fenretinide has provenclinical tolerability at plasma doses of 1-18 uM when given orally using a 100 mg capsule (NCI, IND#40294). However, the current 4-HPR oral capsule has low bioavailability, produces wide interpatient variability in peak and steady-state plasma levels, and is difficult to deliver in patients <4 years of age. Thus, 4-HPR pharmacokinetics and tumor response may benefit from an improved formulation of delivery. In an attempt to improve the antitumor activity of 4-HPR, a novel oral 4-HPR powder formulation (4-HPR/LXS oral powder, -3% by weight 4-HPR) has beenprepared based on a lipid matrix technology, called Lym-X-Sorb (LXS). 4-HPR/LXS oral powder is suitable for delivery in non-milk fat-containing foods, and especially as a slurry in non-milk fat-containing, or soy-based nutritional supplements, such as Slim-Fast Meal.